tbuckley/cabot-search huggingface dataset:
P109: One-Day Brentuximab-Bendamustine (120mg/m2) every 21 days is a feasible and safe treatment for relapsed/refractory Hodgkin lymphoma
Authors: Hannah Moatti, Marie-Céleste Laroque, Loïc. Renaud, Odonchimeg Ravdan, Charlotte Schmidt-Hieber, Isabelle Madelaine, Roberta Di Blasi, Catherine Thieblemont, Pauline Brice
Journal: HemaSphere (2022)

Brentuximab(1.8 mg/kg day 1) plus Bendamustine (90mg/m2 day 1 and 2) every 28 days is a new therapeutic combination for relapsed/refractory (R/R) Hodgkin lymphoma (HL), mainly as salvage therapy and bridge to autologous stem-cell transplantation (ASCT) but is associated to high toxicity. We conducted a retrospective study in St Louis Hospital in Paris between 2015 and 2021 to assess the feasibility and tolerance of one-day Brentuximab-Bendamustine (120mg/m2) every 21 days for R/R HL. All patients for whom one-day Brentuximab-Bendamustine (120mg/m2) every 21 days was prescribed between 2015 and 2021 were identified from the Chimioweb platform and medical data were collected from Middlecare software. Characteristics of population were detailed. Feasibility and toxicities were reported. Progression-free survival (PFS) and overall survival (OS) were calculated. Three patients were excluded (one in complete response at beginning, one who refused therapy and one lost to follow-up with second cancer). Forty-three patients were included, with a median age of 45 years old (19 to 76) at time of treatment. Relapse or progression was of advanced stage for 63% of patients and occurred after a median of 2 former lines. Sixteen patients (37%) had only one line before. Eleven (26%) patients already had an ASCT and 2 (5%) an allogenic stem cell transplantation. Twenty-seven patients (63%) and 12 (28%) had respectively a relapsed or refractory HL. Four patients (9%) had a secondary HL. A median of 5 cycles was administered. For 32 patients (74,4% [95%CI, 74 to 74,8]) treatment was conducted until its end and did not need any adaptation for toxicity. Main causes of adaptation were anaphylaxis (7%), neutropenia (2%), infection (2%) and peripheral neuropathy (2%). Anaphylactic reactions occurred in 16 patients (37%), of which one was grade 3 and no grade 4. For 8 of these patients (50%), reaction was resolved after prescription of pre-medication. Grade 3–4 neutropenia and thrombocytopenia occurred in respectively 3 (7%) and 2 (5%) patients. Only one febrile neutropenia was reported. After treatment, overall response rate was of 84%, with 31 (72%) complete responses, 5 (12%) partial responses, 1 (2%) stable disease and 5 (12%) progressive diseases. We suggest that one-day Brentuximab-Bendamustine (120mg/m2) ever 21 days is a safe and feasible treatment for R/R HL. Main limiting toxicity was anaphylactic reaction, which was well managed with premedication.
P007: Comparative efficacy of the R-BEACOPP-14 and R-CHOP regimens in the treatment of patients with advanced stages of nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) with THRLBCL-like histopathological growth patterns in the tumor biopsy
Authors: Elena Dorokhina, T.N. Moiseeva, A.M. Kovrigina, Irirna Shupletsova, L.S. Al-Radi, Yu. A. Chabaeva, Ya.K. Mangasarova
Journal: HemaSphere (2022)

Introduction: Our data demonstrated an unfavorable prognostic value of THRLBCL-like histopathological growth patterns in the tumor substrate. Differentiated approaches of the therapy of this patients group have not been defined yet. Objective: to evaluate the results of 1st line therapy of advanced stages NLPHL patients with THRLBCL-like histopathological growth patterns in the tumor biopsy, depending on the type of induction chemotherapy program. Materials and methods: Results of 1st line therapy in 150 patients with NLHLP observed from 2010 to 2021 were analyzed. Growth patterns without THRLBCL-like sites was observed in 87/150 (58%) patients, of them 33 (38%) had advanced stages of the disease (AS). THRLBCL-like patterns were in 63/150 (42%), of them 55 (87%) pts with AS. Patterns with predominance of THRLBCL-like areas (more than 50% of the cut area) - 32 (21%), of them 31 (97%) pts with AS. Results: In 33/87(38%) pts with growth patterns without THRLBCL-like areas – chemotherapy was performed in 27/33(81%) pts: R-BEACORP-14 in 17/27(63%), R-ABVD in 10/27(37%), all pts achieved complete remission (CR). In of 55/63(87%) pts with advanced stages and with THRLBCL-like patterns, chemotherapy was underwent in 54/55(98%) pts: R-BEACORP-14–30/54(56%), of them CR - 18/ 30(60%); R-CHOP - 12/54 (21%), of them CR - 4/12 (30%); other - 12/54 (23%) pts. In 31/32(97%) pts with advanced stages and with predominance of THRLBCL-like areas, chemotherapy received 30/31(97%) pts: R-BEACORP-14–17/30(57%), of them CR - 8/17(47%); R-CHOP - 8/30 (27%), of them CR - 2/8 (25%); other - 5/30 (17%) pts. In pts groups with the presence and predominance of THRLBCL-like growth patterns the 5-year OS on the R-BEACOPP-14 scheme was 100% and 62%, and on the R-CHOP - 100% and 69% (p-0.02), respectively. The 3-year EFS on the R-BEACORP-14 scheme was 91% and 44%, and on the R-CHOP - 50% and 29% (p-<0.0001), respectively. Median follow-up is 34 months. Conclusion: Induction therapy with R-BEACORP-14 allows to achieved the best overall and event-free survival in an unfavorable group of advanced stages NLPHL patients with the presence and predominance of THRLBCL-like growth patterns.
P089: Pembrolizumab in Pediatric and Young Adults Patients With Newly Diagnosed Classical Hodgkin Lymphoma and Slow Early Responders to Frontline Chemotherapy: The Phase 2 KEYNOTE-667 Study
Authors: Luciana Vinti, Stephen Daw, Constantino Sabado Alvarez, Franca Fagioli, Auke Beishuizen, Gerard Michel, Maria Luisa Moleti, Michaela Cepelova, Anne Thorwarth, Charlotte Rigaud, Diego Plaza Lopez De Sabando, Judith Landman Parker, Ying Zhu, Pallavi Pillai, Akash Nahar, Christine Mauz-Koerholz
Journal: HemaSphere (2022)

Background: Slow-early response (SER) to initial chemotherapy (chemo) and added radiotherapy (RT) exposure increases the risk for relapse and toxicity in patients (pts) with classical Hodgkin lymphoma (cHL). Pediatric and young adult pts with cHL and SER received pembrolizumab (pembro) + chemo in the open-label, phase 2 KEYNOTE-667 study (NCT03407144). We present interim data in pts with high-risk cHL (group 2) and SER to frontline chemo. Methods: Eligible pts in group 2 were aged 3–25 y with newly diagnosed stage IIEB, IIIEA, IIIEB, IIIB, IVA, or IVB cHL. After 2 cycles of vincristine, etoposide, prednisone/prednisolone, doxorubicin (OEPA), pts with SER (Deauville score 4 or 5) received ≤17 doses of pembro 2 mg/kg to 200 mg (3–17 y) or 200 mg (18–25 y) IV Q3W + 4 cycles of cyclophosphamide, vincristine, prednisone/prednisolone, dacarbazine (COPDAC-28). After COPDAC-28 consolidation, pts with SER and were PET-positive (Deauville score 4 or 5) received RT + ≤17 doses of pembro; pts with SER and were PET-negative (Deauville score 1–3) received only pembro for ≤17 doses. Safety analyses included pts with SER who received ≥1 dose of pembro; efficacy analyses included pts who completed post-COPDAC-28 response assessment. The primary end point was ORR by blinded independent central review (BICR) per IWG 2007 criteria in pts with SER. Secondary end points included post-COPDAC-28 PET-negative rate, RT exposure details, and safety. Data cutoff was Nov 22, 2021. Results: Group 2 included 30 pts with high-risk cHL; median age was 15 y (range, 6–19), 13 (43%) pts had bulky disease, and 19 (63%) had Ann Arbor stage IV disease. At data cutoff, 23 (77%) pts had adverse events (AEs) and 6 (20%) had AEs grade ≥3; 14 (47%) pts had treatment-related AEs (TRAE) and 2 (7%) had TRAEs grade ≥3. Serious AEs occurred in 3 (10%) pts (1 [3%] pt had grade 2 immune-mediated hypothyroidism). After 9.6 mo (range, 2.5–21.2) of median follow-up, 6 (20%) pts completed and 24 (80%) were continuing treatment; median time on treatment was 3.3 mo (range, 0–11.8). Of the 25 (83%) pts who had a post-COPDAC-28 assessment, 17 (68%) were PET-negative by BICR; 18 (72%) pts by investigator assessment. Conclusion: Pembro + COPDAC-28 in pediatric and young adult pts with high-risk cHL and SER to frontline chemo demonstrated acceptable safety. Thus, 68% of pts with PET-negative response were spared RT after consolidation. Early data show that pembro may enhance responses to chemo in this pt population.
P056: Variants of the transcription factor ONECUT2 regulate gene expression in Hodgkin Lymphoma cells
Authors: Patricia Lein, Charles Gwellem Anchang, Ines Volkmer, Martin S. Staege
Journal: HemaSphere (2022)

Background: ONECUT transcription factors are characterized by the presence of a single CUT domain and a HOX domain. ONECUT2 is involved in pathogenesis of several solid tumors and regulates proliferation, migration and differentiation of tumor cells. We identified a transcript variant of ONECUT2 in a cDNA library of the chemo-resistant Hodgkin lymphoma (HL) cell line L-1236. This variant (ONECUT2s) contains a CUT Domain without a corresponding HOX domain. To further characterize this variant, we performed over-expression and knock-down studies in diverse cell line models and studied the impact of ONECUT2 variants on gene expression. Methods: Expression of ONECUT2 and ONECUT2s in tissue samples and cell lines was assessed by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Additional expression studies were performed using public available microarray data sets. RNA interference was used for knock-down of ONECUT2 and ONECUT2s. For over-expression studies, the different ONECUT2 variants were cloned into the doxycycline-inducible vector pRTS-1, with a bi-directional promoter, allowing simultaneous expression of the transgene and the reporter EGFP. Knock-down and over-expression was analyzed by qRT-PCR. For assessing the influence of ONECUT2 and ONECUT2s on gene expression, microarray analysis and RNA-seq analyses were performed. Results: Gene expression analysis by qRT-PCR showed high expression of ONECUT2 and ONECUT2s in HL-cell lines and normal liver. Public available microarray data also indicated high expression of ONECUT2 in HL-cell lines and a subset of HL biopsies. The majority of the other tissues and cell lines showed only low expression of both ONECUT2 variants. Microarray and RNA-seq analyses of transgenic cells and cells after knock-down of ONECUT2 variants showed that both variants affected the global gene expression profile. However, effects of ONECUT2 were much stronger than effects of ONECUT2s. Both variants seem to regulate different sets of genes, especially for ONECUT2 these genes include genes involved in apoptosis regulation and immune response. Conclusion: ONECUT2 acts as a transcription factors in HL-cells and both variants have different effects on gene expression. The high expression of both ONECUT2 variants in HL might qualify this transcription factor as a possible candidate for targeted therapy of HL. Our work is supported by Mitteldeutsche Kinderkrebsforschung
T065: Reproduction patterns among Classical Hodgkin Lymphoma Survivors Treated with BEACOPP and ABVD in Sweden, Denmark, and Norway
Authors: Joshua P. Entrop, Caroline E. Weibull, Karin E. Smedby, Lasse Hjort Jakobsen, Andreas K. øvlisen, Daniel Molin, Ingrid Glimelius, Anna Marklund, Harald Holte, Alexander Fosså, Knut B. Smeland, Tarec Christoffer El-Galaly, Sandra Eloranta
Journal: HemaSphere (2022)

Figure 1: Aalen-Johansen estimates of the cause-specific cumulative incidence (CIF) of childbirth estimated in the presence of competing risks of death. Background: Reproduction in classical Hodgkin lymphoma (cHL) survivors has been shown to be reduced compared to the general population, likely due to multi-agent chemotherapy. Understanding if contemporary treatment protocols are associated with reduced reproduction is important as treatment guidelines shift towards more liberal use of more intensive chemotherapy. Methods: We identified 2,937 individuals aged 18–40 years with cHL in Swedish and Danish lymphoma registers, and in the clinical database at Oslo University Hospital (OUH) between 1995 and 2019, who were linked to national medical birth registers in each country. Cox regression adjusted for stage, performance status, year and age at diagnosis was used to estimate hazard ratios (HRs) contrasting time to first childbirth by treatment groups (ABVD, 2–4 BEACOPP, 6–8 BEACOPP) up to ten years after diagnosis. Cause-specific cumulative incidence (CIF) of childbirths was further estimated using flexible parametric survival models. All analyses included an interaction between cHL treatment and sex. Results: Overall, 71.4% of patients were treated with ABVD, 3.6% with 2–4 BEACOPP, and 10.3% with 6–8 BEACOPP. The reproduction rates (per 1,000 person-years) were 45.5 (males) and 48.2 (females) in the ABVD group, and 23.8 (males) and 39.9 (females) in the 6–8 BEACOPP group. The adjusted HR comparing reproduction rates in individuals treated with 6–8 BEACOPP to ABVD was 0.51 (95% CI 0.35–0.73) for males and 0.82 (95% CI 0.57–1.19) for females. The CIF after 10 years was 20.0% (CI: 14.7%–27.2%) for males and 33.0% (CI: 24.6%–44.3%) for females treated with 6–8 BEACOPP. Conclusion: We found that BEACOPP treatment is associated with decreased reproduction rates compared to ABVD in male cHL patients. Infertility counselling should be prioritized for this group. This abstract has been accepted and presented at the EHA 2022 congress.
P003: A retrospective study to evaluate the reliability of staging and risk stratification of adolescent and adult patients with Hodgkin’s lymphoma registered in the lymphoma clinic at Tata Memorial Centre.
Authors: Hasmukh Jain, Ajay Singh, Manju Sengar, Thomas Eipe, Hiral Mehta, Bhausaheb Bagal, Jayashree Thorat, Lingaraj Nayak, Neha Sharma
Journal: HemaSphere (2022)

Table 1: Baseline characteristics Purpose: Risk stratification is a key factor,which depends on staging, clinical and laboratory parameters in determining the treatment in Hodgkin’s lymphoma (HL). However, this is highly prone to erroneous results due to overlapping components in the staging systems and inter-observer variability.We conducted this study to assess the reliability of risk stratification performed by our clinicians at our busy multidisciplinary clinic (MDC). Methods: A retrospective analysisof newly diagnosed HL patients from the multidisciplinary clinic database for the year 2016-18was conducted.All patients underwent an 18-FDG PET/CT scan and other evaluations as per our institutional checklist. The reliability of staging and risk stratification done during the MDC was compared with a team of independent experts (medical oncology, radiation oncology and nuclear medicine) based on a standard reference. The concordance testing was done using kappa statistic for agreement (≥ 0.8 as perfect agreement) andP <0.05 was considered significant. Results: 120 patients were analyzed, and the baseline characteristics are described in Table 1. The patients initially underwent staging by MDC and were risk stratified into early favorable (16 patients [13.5%]), early unfavorable (29 patients [24%]) and advanced (75 patients [62.5%]). A discordance rate of 10% (12 patients) was observed in disease staging and 8.3% in risk stratification (10 patients) between the MDC and the expert team. All deviations were due to up-staging of patients by MDC, of which 9 patients in early favorable were misclassified as early unfavorable and 1 patient as advanced from early unfavorable. This resulted in 10 patients receiving higher dose of chemotherapy and radiation. However, no patients were under treated. On completion of treatment, 82%of patientshadcomplete response, 12%had partial responseand 5%had disease progression. Our results show that the discordance rates were not significantbetween the independent reviewers and MDC team with kappa score of 0.859 for stagingand 0.847 for risk stratification. Conclusion: Despite our busy setting, the risk stratification was found to be reliable and comparable to reference standards. One reason for this would be the involvement of a multidisciplinary team in our lymphoma clinic. Yet, 8% of the patients received a more intense therapy than needed, demonstrating the need for a simpler, objective and technology driven risk stratification process.
P004: Advanced stage classical Hodgkin lymphoma (cHL) patients with a positive interim-PET (PET-2) Deauville score (DS) 5 after 2 ABVD cycles: A pooled analysis of individual patient data of three multicenter trials
Authors: Simonetta Viviani, Chiara Pavoni, Sally F. Barrington, Luca Guerra, Heiko Schöder, Peter Johnson, Amy A. Kirkwood, Deborah M. Stephens, Jonathan W. Friedberg, Stephane Chauvie, Michael V. Knopp, Massimo Federico, Gunilla Enblad, Paolo Corradini, Andrea Gallamini, Alessandro Rambaldi, Corrado Tarella
Journal: HemaSphere (2022)

Background: PET-2 is widely adopted to select patients (pt) with advanced-stage cHL, who might benefit from intensifying or de-escalating therapy. Improved PFS has been reported in PET-2 positive pt switched from ABVD to escalated BEACOPP (eBEACOPP) compared to historical controls continuing ABVD. Nevertheless, pt with a PET-2 Deauville score (DS) 5 have a dismal prognosis, with PFS from 35% to 50% at 3 years despite treatment intensification. Aim of Study: To refine outcome prediction, we conducted a pooled analysis of individual pt data from 3 multicenter trials: HD0607 GITIL/FIL, RATHL and SWOG S0816 focusing on pt with PET-2 DS 5 after ABVD who had intensified treatment with eBEACOPP or BEACOPP-14. Methods: The prognostic value of clinical characteristics, laboratory parameters, metabolic tumor volume (MTV) and total lesion glycolysis (TLG) at diagnosis was evaluated. MTV was calculated with an automatic software segmentation using SUV 4.0 threshold in each pt. Predictive factors of PFS measured from the date of PET-2 until progression, relapse, death from any cause or last follow-up, and overall survival (OS) were analyzed using Cox regression. Baseline characteristics and PET MTV/TLG of pt who failed vs those who achieved CR with intensified treatment were compared. Results: Among 2231 pt with available PET scans for review, 136 (6%) PET-2 DS 5 pt were included in the study: M 72, F 64, median age 34 yrs, Nodular Sclerosis 71%, stage IIB/III/IV 29%/ 22% /49%, B symptoms 72%, IPS >3: 31%; bulky 22%; neutrophil/lymphocyte ratio > 6: 61%. At baseline median MTV and TLG were 243 cm3 (range, 1.6–4266) and 1476cm3 (range, 7.3–29386). After a median follow-up of 41 months, 3-yr PFS and OS were 32% (95% CI, 25–42) and 82% (95% CI, 75–89), respectively. In univariate analysis no clinical or laboratory parameter nor MTV was significantly associated with PFS, whereas age ≥ 45 years, median numbers of leukocytes, lymphocytes and monocytes were significantly associated with OS. Using a threshold of 192 cm3 for MTV calculated by Youden index, 3-year PFS and OS were 35% and 87% vs 34% and 79% for pt with low vs high MTV (p=ns). Conclusions: Pt with PET-2 DS 5 after ABVD receiving intensified treatment have similar outcomes to refractory disease with only 32% 3-yr PFS. No factors measured at diagnosis were able to detect the later failures within the DS 5 cohort. Nevertheless, pt receiving PET-guided treatment intensification can benefit from a prolonged OS.
P073: Increased risk of colorectal cancer following treatment for Hodgkin lymphoma
Authors: Yvonne M.G. Geurts, Rebecca Shakir, Georgios Ntentas, Sander Roberti, Marianne Aznar, Katinka John, Johanna Ramroth, Cécile P.M. Janus, Augustinus Krol, Judith Roesink, Richard W.M. Van Der Maazen, Josée. M. Zijlstra, Sarah Darby, Berthe M. P. Aleman, Flora E. Van Leeuwen, David Cutter, Michael Schaapveld
Journal: HemaSphere (2022)

Purpose: Hodgkin lymphoma (HL) survivors have an increased colorectal cancer (CRC) risk, which may be related to subdiaphragmatic radiation and/or alkylating chemotherapy. While radiation dose-response relationships for breast, lung, stomach, pancreas and esophagus cancer after HL have been demonstrated, no previous studies have investigated this for CRC after HL. This study aimed to quantify CRC rate according to radiation dose to the large bowel and procarbazine dose. Methods: We conducted a nested case-control study among 2996 five-year HL survivors treated in 1965–2000 at ages 15–50 years, who were followed for a median duration of 26.1 years. Treatment information was collected for 78 CRC cases and 238 controls, individually matched on sex, age at HL diagnosis and date of HL diagnosis. Mean radiation doses to the large bowel were estimated by reconstructing individual radiotherapy treatments on representative computed tomography datasets. Rate ratios (RRs) were estimated using conditional logistic regression. Excess rate ratios (ERRs) were modelled to evaluate the excess rate associated with each gray increase in radiation dose and effect modification by procarbazine was explored. Results: The median age at HL diagnosis was 33.0 years and the median interval between HL and CRC was 25.7 years. Increased CRC rates were seen for patients who received subdiaphragmatic radiation (RR 2.4; 95% confidence interval (CI) 1.4–4.1) and those who received >8.4 g/m2 procarbazine (RR 2.5; 95% CI 1.3–5.0). Overall, CRC rate increased linearly with mean radiation dose to the whole large bowel and dose to the affected bowel segment. The effect of radiation dose on CRC rate was modified by cumulative procarbazine dose: the ERR/gray to the whole large bowel was 3.5% (95% CI 0.4–12.6%) for patients who did not receive procarbazine, and increased 1.19-fold (95% CI 1.06–1.33) for each g/m2 increase in procarbazine dose, with an ERR/gray of 15.0% for patients who received 8.4 g/m2 procarbazine. Conclusion and relevance: This is the first study to demonstrate a dose-response relationship between radiation and CRC risk, and modification of this effect by procarbazine. Results enable individualized CRC risk estimations, identification of high-risk survivors and optimization of treatment strategies for future patients.